Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells
The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban), a n...
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Elsevier
2015-01-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750015300512 |
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| author | Sheng-Nan Wu Hui-Zhen Chen Yu-Hung Chou Yan-Ming Huang Yi-Ching Lo |
| author_facet | Sheng-Nan Wu Hui-Zhen Chen Yu-Hung Chou Yan-Ming Huang Yi-Ching Lo |
| author_sort | Sheng-Nan Wu |
| collection | DOAJ |
| description | The nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban), a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa) channels, namely, large-conductance KCa (BKCa) and intermediate-conductance KCa (IKCa) channels, were investigated in Madin–Darby canine kidney (MDCK) cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo. |
| first_indexed | 2024-12-11T07:06:29Z |
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| id | doaj.art-713ee050029948fbb242652e8f7ef556 |
| institution | Directory Open Access Journal |
| issn | 2214-7500 |
| language | English |
| last_indexed | 2024-12-11T07:06:29Z |
| publishDate | 2015-01-01 |
| publisher | Elsevier |
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| series | Toxicology Reports |
| spelling | doaj.art-713ee050029948fbb242652e8f7ef5562022-12-22T01:16:29ZengElsevierToxicology Reports2214-75002015-01-012C1182119310.1016/j.toxrep.2015.08.010Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cellsSheng-Nan Wu0Hui-Zhen Chen1Yu-Hung Chou2Yan-Ming Huang3Yi-Ching Lo4Department of Physiology, National Cheng Kung University Medical College, Tainan City, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan City, TaiwanSchool of Medicine, Mayne Medical School, University of Queensland, Brisbane, Queensland, AustraliaDepartment of Physiology, National Cheng Kung University Medical College, Tainan City, TaiwanDepartment of Pharmacology, Kaohsiung Medical University, Kaohsiung City, TaiwanThe nitrogen-containing bisphosphonates used for management of the patients with osteoporosis were reported to influence the function of renal tubular cells. However, how nitrogen-containing bisphosphates exert any effects on ion currents remains controversial. The effects of ibandronate (Iban), a nitrogen-containing bisphosphonate, on ionic channels, including two types of Ca2+-activated K+ (KCa) channels, namely, large-conductance KCa (BKCa) and intermediate-conductance KCa (IKCa) channels, were investigated in Madin–Darby canine kidney (MDCK) cells. In whole-cell current recordings, Iban suppressed the amplitude of voltage-gated K+ current elicited by long ramp pulse. Addition of Iban caused a reduction of BKCa channels accompanied by a right shift in the activation curve of BKCa channels, despite no change in single-channel conductance. Ca2+ sensitivity of these channels was modified in the presence of this compound; however, the magnitude of Iban-mediated decrease in BKCa-channel activity under membrane stretch with different negative pressure remained unchanged. Iban suppressed the probability of BKCa-channel openings linked primarily to a shortening in the slow component of mean open time in these channels. The dissociation constant needed for Iban-mediated suppression of mean open time in MDCK cells was 12.2 μM. Additionally, cell exposure to Iban suppressed the activity of IKCa channels, and DC-EBIO or 9-phenanthrol effectively reversed its suppression. Under current-clamp configuration, Iban depolarized the cells and DC-EBIO or PF573228 reversed its depolarizing effect. Taken together, the inhibitory action of Iban on KCa-channel activity may contribute to the underlying mechanism of pharmacological or toxicological actions of Iban and its structurally similar bisphosphonates on renal tubular cells occurring in vivo.http://www.sciencedirect.com/science/article/pii/S2214750015300512IbandronateMDCK cellLarge-conductance Ca2+-activated K+ channelIntermediate-conductance Ca2+-activated K+ channelMembrane potential |
| spellingShingle | Sheng-Nan Wu Hui-Zhen Chen Yu-Hung Chou Yan-Ming Huang Yi-Ching Lo Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells Toxicology Reports Ibandronate MDCK cell Large-conductance Ca2+-activated K+ channel Intermediate-conductance Ca2+-activated K+ channel Membrane potential |
| title | Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells |
| title_full | Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells |
| title_fullStr | Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells |
| title_full_unstemmed | Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells |
| title_short | Inhibitory actions by ibandronate sodium, a nitrogen-containing bisphosphonate, on calcium-activated potassium channels in Madin–Darby canine kidney cells |
| title_sort | inhibitory actions by ibandronate sodium a nitrogen containing bisphosphonate on calcium activated potassium channels in madin darby canine kidney cells |
| topic | Ibandronate MDCK cell Large-conductance Ca2+-activated K+ channel Intermediate-conductance Ca2+-activated K+ channel Membrane potential |
| url | http://www.sciencedirect.com/science/article/pii/S2214750015300512 |
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